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Background. Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury. At least 1% to 5% will suffer a stroke, and at 3-months postoperatively approximately 30% are reported to have cognitive impairment assessed by neuropsychologic testing. In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced. The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization. Methods. This was a prospective and randomized study of two comparable groups with regard to age, sex, years of education, preoperative cognitive functioning, and surgical characteristics. Fifty-two patients (29 off-pump) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery. Preoperative and postoperative clinical, cerebral magnetic resonance imaging, and neuropsychologic examinations were also carried out. Results. There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery (16.3 [range 0 to 131] versus 90.0 [range 15 to 274], p < 0.0001). No significant difference with regard to the incidence of neuropsychologic performance (decline in 29% off-pump, 35% on-pump) or neuroradiologic findings at 3 months was found, and there was no association between the number of cerebral microemboli and cognitive outcome. Conclusions. This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization. A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population.